Effectiveness and Safety of Epilepsy Surgery for Pediatric Patients with Intractable Epilepsy: A Clinical Retrospective Study from a Single-Center Experience.

INTRODUCTION: Pediatric epilepsy surgery is an effective treatment modality for patients with drug-resistant epilepsy (DRE). Early pediatric surgery yields favorable results for DRE in terms of seizure control and neurophysiological outcome. In this study, pediatric patients were categorized based on their age (above 3 years old and below 3 years old) to demonstrate the effectiveness and safety of surgical procedures. METHODS: In this retrospective, single-center study, 60 pediatric patients who underwent epilepsy surgery at Istanbul Faculty of Medicine between 2002 and 2018 were evaluated. Overall morbidity and mortality rates, as well as seizure outcomes of the patients, were assessed and compared based on two age groups: those aged 3 years old or younger and those older than 3 years old. The effectiveness of invasive monitoring was also evaluated in relation to pathological results. The postoperative seizure outcome rates were evaluated using Engel's classification, with an average follow-up period of 8.7 years. RESULTS: Out of the total number of patients, 47 (78.4%) underwent resective surgery, while 13 (21.6%) had palliative surgery. Ten patients (16.6%) had invasive monitoring. Among all patients, 34 were classified as Engel I and II (56.6%), while 26 were classified as Engel III and IV (43.4%) postoperatively. 47% of patients who were under 3 years old, 60.4% of patients who were over 3 years old, and 50% of patients who underwent invasive monitoring had a favorable seizure outcome (Engel I-II). Postoperative morbidity and mortality rates were 35% (n = 21) and 1.6% (n = 1), respectively. CONCLUSION: Pediatric epilepsy surgery is an important treatment modality for preserving cognitive abilities and providing effective treatment for pediatric DRE. In our study, we claim that both invasive monitoring and epilepsy surgery lead to favorable seizure outcomes for all age groups. Further clinical studies should be conducted to provide more reliable data on the safety and effectiveness of the surgery, particularly in patients under the age of three.

Focal cortical dysplasia pathology: diagnostic difficulty, classification, and utility for pathogenesis.

OBJECTIVE: In the histopathological examination of treatment-resistant epilepsy, focal cortical dysplasia (FCD) is the most common diagnosis in the pediatric group. FCD is classified histopathologically according to the International League Against Epilepsy (ILAE) classification. In the last decade since the ILAE classification has been released, molecular genetic studies have revealed mTOR pathway-related mutations as a major etiology. The objective of this study was to determine the incidence of FCD in treatment-resistant epilepsy patients, explore histomorphological and immunohistochemical features, examine clinicopathological correlation, demonstrate mTOR pathway activation using a pS6 antibody immunohistochemically, and try to introduce a candidate for possible targeted therapies. METHODS: Paraffin blocks and slides of tissue from patients with treatment-resistant epilepsy were reexamined retrospectively. Histopathological subtypes of FCD were determined according to the ILAE classification. NeuN and neurofilament H (NF-H) staining were performed, and additionally a pS6 antibody was used to demonstrate mTOR pathway activation. RESULTS: In 32 cases diagnosed with FCD, or 17.5% of 183 surgical epilepsy materials, there were no significant differences in the statistical analysis of clinical variables between the ILAE FCD subtypes. Recommended antibody NeuN revealed microcolumnar alignment in the FCD type Ia and IIIa groups and the loss of lamination in the type Ib group. Another recommended antibody, NF-H, was not found to be useful in discriminating between normal and dysmorphic neurons. pS6 expression, showing mTOR pathway activation, was observed in dysmorphic neurons and balloon cells in all FCD type II cases. CONCLUSIONS: Significant pS6 expression in FCD type II represents the genomic nature of the disease noted in the literature. Nevertheless, the known MTOR gene and mTOR pathway-related mutations remain behind proportionally to explain the mTOR pathway activation in all FCD type II cases. Clinicopathologically and genetically integrated classification and usage of mTOR pathway inhibitors in treatment are expected as a recent evolution.

An Investigation into the Correlation of Scalp Electrophysiological Findings with Preoperative Clinical and Imaging Findings in Patients with Focal Cortical Dysplasia.

AIM: To evaluate the patients who had epilepsy surgery and pathologically proven focal cortical dysplasia (FCD) in order to further classify and discuss electroencephalography (EEG) findings in different pathological subtypes. MATERIAL AND METHODS: This study included 19 refractory epilepsy patients who underwent surgery between 1999 and 2017 in the Istanbul Faculty of Medicine. Demographic data, preoperative examinations, scalp video EEGs, and postoperative outcomes were evaluated retrospectively. RESULTS: In this study, 36.8% of the patients were female. The mean age was 21.89 ± 14.64 years. Rhythmic epileptiform discharges (RED) were observed in 31.6%. 37.5% of the patients with isolated intermittent spike/sharp waves were type I, 50% were type II, and 12.5% were type III. 100% of the patients with normal background activity were FCD type II. 67% of the patients with asymmetric slowing were FCD type I, 22% was FCD type II, 11% were FCD type III. 71% of the patients with symmetrical slowing were FCD type I, 29% were FCD type II. One patient had Frontal Intermittent Rhythmic Activity, one patient had Electrical Status Epilepticus in Slow Sleep, two patients had "burst suppression," and one patient had a "switch of" sign. The frequency of focal epileptogenic activity was higher when there was an FCD lesion on magnetic resonance imaging. CONCLUSION: The findings obtained in this study did not reveal any distinctive electrophysiological features in FCD and subgroups of FCD. The incidence of REDs did not differ between types. The frequency of isolated intermittent sharp/spike waves was higher in type II than I. Intermittent and continuous EEG slowing was more commonly seen among FCD Type I patients.

Surgical Treatment in Refractory Epilepsy: Seizure Outcome Results Based on Invasive EEG Monitorization.

AIM: To discuss seizure outcomes of patients with invasive electroencephalography (EEG) monitorization (IEM) following their epilepsy surgery at our centre. MATERIAL AND METHODS: Forty-seven patients suffering from refractory epilepsy and who were evaluated by invasive EEG were included in this retrospective study at Istanbul Faculty of Medicine from 2003 to 2017. We examined the Video EEG and invasive EEG monitorization, cranial MRI, SPECT, PET and neuropsychological tests of all patients. Postoperative seizure outcome results were evaluated according to Engel classification. The factors affecting seizure outcomes were discussed. RESULTS: Twenty-six of the patients were female (55.3%), 21 were male (44.7). The average age was 32.0 (± 12.4). Forty-three patients had surgery and the average age of these patients was 26,6 (±11.15). 38.3% of the patients had hippocampal sclerosis (HS), 23.4% had focal cortical dysplasia (FCD), 8.5% had a tumor, 14.9% had sequela lesion and 14.9% had unknown etiology. Postoperative seizure status according to the Engel classification showed that 81.6% of the patients were class I, 10.5% were class II, 2.6% were class III and 5.3% were class IV. CONCLUSION: A significant relation was statistically determined between structural MRI lesion and favorable seizure outcome (p < 0.05). The most frequent etiology was HS in our patients. Of the patients with Engel I, the averages of their ages, ages at onset of epilepsy and ages at surgery were lower than other groups, but the difference was not statistically significant (p > 0.05). We argue that IEM is an essential examination for favorable outcomes for determining the epileptogenic zone and/or the proximity of the functional structures.

Depression is a major determinant of sleep abnormalities in patients with epilepsy / A depressão é um dos principais determinantes das anormalidades do sono em pacientes com epilepsia

ABSTRACT Introduction: We aimed to identify sleep disorders in patients with epilepsy and compare this group with a healthy population. We also analyzed the features of sleep disorders in patients with epilepsy to demonstrate the effect of seizures and seizure types on sleep. Methods: Our study assessed 43 patients with epilepsy and 53 age- and gender-matched healthy controls. The demographic and clinical data of all participants were recorded. The Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI), International Restless Legs Syndrome Study Group Rating Scale, Berlin Questionnaire, and Beck Depression Inventory (BDI) were administered to all study subjects. The interview used to evaluate insomnia is based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition - DSM-5 diagnostic criteria. Results: Twenty-four patients (55.8%) and 26 controls (49.1%) are women. The mean age of patients and controls was 34.2±11.37 (16-71) and 34.6±11.28 (16-77), respectively. Patients with epilepsy had depression more often than controls, a result that was statistically significant (p<0.0001). We found no statistically significant difference between sleep parameters of patients and controls with normal BDI scores (p>0.05). Patients with depression had worse results on the Berlin Questionnaire and PSQI total score, with statistical significance (p=0.002). Nocturnal seizures, seizure type, and drug treatment had no effect on sleep (p>0.05). Conclusion: We concluded that depression rather than epilepsy negatively affects sleep, suggesting that all patients should be asked about their mood and sleep complaints.

RESUMO Introdução: O objetivo deste estudo foi identificar distúrbios do sono em pacientes com epilepsia e compará-los com uma população saudável. Também foram examinadas as características dos distúrbios do sono em pacientes com epilepsia para demonstrar o efeito e os tipos de convulsões no sono. Métodos: O estudo consistiu em 43 pacientes com epilepsia e 53 controles saudáveis ​​pareados por idade e sexo. Os dados demográficos e clínicos de todos os participantes foram registrados. Todos os participantes do estudo receberam a Escala de Sonolência de Epworth, o Índice de Qualidade do Sono de Pittsburgh (Pittsburch Sleep QUality Index - PSQI), o Questionário do Grupo Internacional de Estudos das Pernas Inquietas, o Questionário de Berlim e o Inventário de Depressão de Beck. A entrevista usada para avaliar a insônia é baseada nos critérios do DSM-V. Resultados: Vinte e quatro pacientes (55,8%) são do sexo feminino e vinte e seis do grupo controle (49,1%) são do sexo feminino. A média de idade dos pacientes e do grupo controle é de 34,2±11,37 (16-71) e 34,6±11,28 (16-77), respectivamente. Pacientes com epilepsia sofrem mais de depressão do que os controles e esse resultado é estatisticamente significativo (p<0,0001). Não houve diferença estatisticamente significativa entre os parâmetros do sono dos pacientes e dos controles que apresentaram escores de Beck normais (p>0,05). Pacientes com depressão apresentam resultados piores no escore total do PSQI de Berlim, o que é estatisticamente significativo (p=0,002). As convulsões noturnas, o tipo de convulsão e o tratamento medicamentoso não afetaram o sono (p>0,05). Conclusão: Determinamos que a depressão, e não a epilepsia, afeta negativamente o sono dos pacientes, sugerindo que todos os pacientes devem ser questionados sobre seu humor e queixas de sono.

The Impact of Affective State on Quality of Life in Focal Epilepsy in Turkey.

CONTEXT: Seizures and accompanying situations including social, medical, and psychiatric problems threaten the quality of life (QOL) in patients with epilepsy. The World Health Organization defines health is a state of complete physical, mental, and social well-being, and not merely the absence of disease or infirmity. AIMS: This study examines the prevalence of both depression and anxiety symptoms and also impact of the affective state on QOL in patients with focal epilepsy in Turkey. SETTINGS AND DESIGN: One hundred and five patients with focal epilepsy over 18 years old were included in this study. The patients were classified into four groups according to the presence of AS and seizure control. SUBJECTS AND METHODS: Patients' affective symptoms (AS) and QOL were examined using the Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and QOL in Epilepsy Inventory-31 (QOLIE-31). STATISTICAL ANALYSIS USED: We used descriptive statistics, Chi-square test, independent samples t-test, one-way analysis of variance, Mann-Whitney U-test, Kruskal-Wallis H-test, and also Pearson's and Spearman's correlation test for correlations. RESULTS: There were positive correlations between total QOLIE-31 score and epilepsy surgery, employment, and seizure freedom, whereas negative correlations were found with antiepileptic drug use, anxiety, and depression. Statistically significant differences were found in QOLIE-31 totals and subscores between Groups 3 and 4 (P < 0.05). CONCLUSIONS: The presence of AS has a negative impact on QOL in patients with focal epilepsy. Physicians should be aware that psychiatric comorbidities in epilepsy have a severe impact and epilepsy treatment requires comprehensive management.

Investigation of the Video-EEG Findings and Clinical Data in Patients Diagnosed With Epilepsy and Psychosis.

BACKGROUND: Studies on electrophysiological characteristics of patients with epilepsy and concomitant psychosis are limited. We aimed to investigate the clinical and video-electroencephalography (EEG) findings of patients with epilepsy-related psychosis (EP). MATERIALS AND METHODS: Fifteen patients diagnosed with EP, assessed at the video-EEG monitoring unit and were under follow-up at both epilepsy and psychiatry clinics, were included. A total of 67 nonpsychotic epilepsy patients, investigated at the video-EEG monitoring unit were randomly selected as the control group and compared statistically with the EP group. RESULTS: In medical history, patients with EP had experienced significantly higher level of status epilepticus (P=0.002) and perinatal cerebral injury (P=0.04), whereas drug-resistant epilepsy was detected at a lower level (P=0.015). With respect to seizure onset zone, the EP group had significantly more seizures of unknown foci, whereas the control group had mostly temporal lobe origin (P=0.0004). EEG findings showed that slow background activity was significantly common among patients with EP (P=0.009). Although only 5 of 15 patients with EP had been operated, 43 of 67 patients had undergone epilepsy surgery (P=0.04) in the control group. However, there was no significant difference between the 2 groups with respect to postoperative seizure control as per Engel classification. CONCLUSIONS: Although our sample size could be considered small, slowed EEG background activity, and the marked frequency of initial precipitant factors such as status epilepticus, perinatal cerebral injury, and detected neuronal autoantibodies suggested that EP is associated with more extensive involvement. EP is not a contraindication for epilepsy surgery, when appropriately investigated preoperatively.

Unusual ictal propagation patterns suggesting poor prognosis after temporal lobe epilepsy surgery: Switch of lateralization and bilateral asynchrony.

OBJECTIVE: The objective of this study was to investigate unusual ictal propagation patterns in patients with drug-resistant temporal lobe epilepsy (TLE) and reveal their electrophysiological, neuroimaging, and prognostic properties after surgery. METHODS: Among 248 patients with TLE who underwent scalp video-electroencephalographic (EEG) monitoring, 24 patients with 'switch of lateralization' or 'bilateral asynchrony' in at least one of their seizures (9.3%) were analyzed retrospectively. The postoperative outcome was determined in 16 patients who had undergone epilepsy surgery. RESULTS: All but 5 of the included patients had hippocampal sclerosis (HS) as their magnetic resonance imaging (MRI) findings. Twelve out of 16 patients (75%) who had surgery were seizure-free for at least 1 year. Nine out of 12 patients (75%) with good outcome had unilateral interictal EEG discharges in temporal regions whereas 3 out of 4 patients with poor outcome had bilateral temporal interictal spiking (p = 0.018). CONCLUSION: Unusual ictal propagation patterns are not always related to poor prognosis after surgery in patients with TLE. Patients with unilateral interictal spiking in the temporal region tend to have good outcome despite these unusual patterns. These patterns can also be seen in patients with TLE with other etiologies besides the well-known HS in MRI.

Neurosurgical treatment of nonconvulsive status epilepticus due to focal cortical dysplasia.

We present a rare case of focal cortical dysplasia (FCD) and nonconvulsive status epilepticus (NCSE) treated successfully with early surgical intervention. Our case is a 9-year-old boy whose seizures, characterized by short episodes of loss of consciousness, appeared at the age of 7, and he showed progressive cognitive decline in the following years. NCSE was diagnosed, and his MRI revealed FCD in the left frontal region which was the same side as his EEG abnormality. Following lesionectomy, his NCSE disappeared and cognitive functions improved. Histopathologic analysis of the resected tissue revealed type-IIB FCD. This case illustrates the importance of early surgery to help restore cognitive functions by eliminating the clinical and electrophysiological features of NCSE.

Characterization of Hand Clenching in Human Sensorimotor Cortex Using High-, and Ultra-High Frequency Band Modulations of Electrocorticogram.

Functional mapping of eloquent cortex before the resection of a tumor is a critical procedure for optimizing survival and quality of life. In order to locate the hand area of the motor cortex in two patients with low-grade gliomas (LGG), we recorded electrocorticogram (ECoG) from a 113 channel hybrid high-density grid (64 large contacts with diameter of 2.7 mm and 49 small contacts with diameter of 1 mm) while they executed hand clenching movements. We investigated the spatio-spectral characteristics of the neural oscillatory activity and observed that, in both patients, the hand movements were consistently associated with a wide spread power decrease in the low frequency band (LFB: 8-32 Hz) and a more localized power increase in the high frequency band (HFB: 60-280 Hz) within the sensorimotor region. Importantly, we observed significant power increase in the ultra-high frequency band (UFB: 300-800 Hz) during hand movements of both patients within a restricted cortical region close to the central sulcus, and the motor cortical "hand knob." Among all frequency bands we studied, the UFB modulations were closest to the central sulcus and direct cortical stimulation (DCS) positive site. Both HFB and UFB modulations exhibited different timing characteristics at different locations. Power increase in HFB and UFB starting before movement onset was observed mostly at the anterior part of the activated cortical region. In addition, the spatial patterns in HFB and UFB indicated a probable postcentral shift of the hand motor function in one of the patients. We also compared the task related subband modulations captured by the small and large contacts in our hybrid grid. We did not find any significant difference in terms of band power changes. This study shows initial evidence that event-driven neural oscillatory activity recorded from ECoG can reach up to 800 Hz. The spatial distribution of UFB oscillations was found to be more focalized and closer to the central sulcus compared to LFB and HFB. More studies are needed to characterize further the functional significance of UFB relative to LFB and HFB.

Delta Brush Pattern Is Not Unique to NMDAR Encephalitis: Evaluation of Two Independent Long-Term EEG Cohorts.

PURPOSE: Although its specificity has not previously been investigated in other cohorts, delta brush pattern (DBP) is increasingly reported in the EEGs of patients with anti- N-methyl-d-aspartate receptor (NMDAR) encephalitis. METHODS: We aimed to investigate the DBP in the EEGs of 2 cohorts; patients with change in consciousness for various causes monitored in the intensive care unit (ICU) (n = 106) and patients with mesial temporal lobe epilepsy (MTLE) with or without antineuronal antibodies (n = 76). RESULTS: These patients were investigated for the presence of DBP, defined as an EEG pattern characterized by delta activity at 1 to 3 Hz with superimposed bursts of rhythmic 12- to 30-Hz activity. Two investigators blindfolded for the clinical and immunological data independently analyzed the EEGs for recognition of this pattern. An EEG picture compatible with DBP was observed in 4 patients; only 1 of them (1.3%) belonged to the MTLE group. She did not bear any of the investigated autoantibodies and was seizure-free after epilepsy surgery. In the ICU group, there were 3 additional patients showing DBP with various diagnoses such as hypoxic encephalopathy, brain tumor, stroke, and metabolic derangements. All of them had died in 1-month period. CONCLUSIONS: Our results underlined that DBP is not unique to NMDAR encephalitis; it may very rarely occur in MTLE with good prognosis after surgery and second, in ICU patients who have high mortality rate. Therefore, the presence of this pattern should alert the clinician for NMDAR encephalitis but other possible etiologies should not be ignored.

Investigation of anti-neuronal antibodies in status epilepticus of unknown etiology: a prospective study.

There have been recent reports of antibody-mediated status epilepticus. The objective of our study was to investigate the prevalence of neuronal autoantibodies in patients with status epilepticus (SE) with unresolved etiology. The presence of neuronal autoantibodies was investigated prospectively in adult patients with SE who presented to our clinic between February 2012 and December 2013 with unresolved etiology. Clinical and electrophysiologic features of seropositive patients were recorded. Also, seronegative and seropositive patient groups were compared in terms of demographic and clinical features, treatment responses, and outcomes. Neuronal antibodies against N-methyl-D-aspartate receptor (NMDA-R) were positive in 2 patients, against glycine receptor (Gly-R) in 2 patients, and against gamma-aminobutyric acid-A receptor [GABA(A)R] in 1 patient, which constituted a total of 5 (22.7%) of 22 patients with SE with unidentified etiology. One of three patients with systemic tumors was positive for GABA(A)R antibody. Four patients had a short epilepsy duration, while one of the NMDA-R antibody-positive patients had chronic epilepsy and double cortex finding in MRI. There was no significant difference between seropositive and seronegative patient groups in terms of demographic and clinical features, treatment responses, and outcomes. Neuronal antibodies are found in a sizeable portion of de novo SE patients, who are potential candidates of autoimmune encephalitis. Alternatively, these antibodies may presumably also emerge in SE patients with a chronic epilepsy history as an epiphenomenon. Further research is required to make the distinction between these two different antibody formation mechanisms.

Investigation of neuronal auto-antibodies in systemic lupus erythematosus patients with epilepsy.

PURPOSE: Epilepsy is an important feature for neuropsychiatric involvement in systemic lupus erythematosus (SLE) with unknown mechanism. Our aim was to investigate the presence of neuronal auto-antibodies (NAbs) in neuropsychiatric SLE (NPSLE). METHODS: Eighteen SLE patients (17 females, 1 male) experiencing recurrent seizures were enrolled to this study. Their clinical characteristics, EEG and MRI findings and follow-up information were evaluated from their files. Antibodies against voltage-gated potassium channel (VGKC)-complex antigens, contactin-associated protein-like 2 (CASPR-2), leucine-rich, glioma inactivated 1 (LGI1), glutamic acid decarboxylase (GAD), N-methyl-d-aspartate receptor (NMDA-R), alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor (AMPA-R) and type B gamma aminobutyric acid receptors (GABAB-R) were screened in the sera of these patients. Moreover, indirect immunohistochemistry and immunocytochemistry tests were performed to reveal neuropil antibodies. RESULTS: Six out of 18 patients (33.3%) had various forms of NAbs. Among them, one patient had antibodies against GAD, one patient with hippocampal sclerosis on MRI was CASPR-2 antibody positive, whereas the remaining four patients showed hippocampal neuropil staining. We could not find a significant difference between seropositive and seronegative groups, regarding the clinical characteristics, EEG and MRI findings. CONCLUSION: This study is the first to show hippocampal neuronal staining (4/18) reflecting antibodies against unknown neuronal cell surface antigens in SLE patients with epilepsy, besides the rare occurrence of GAD and CASPR2 antibodies. Further prospective studies are needed to search for new NAbs and uncover their pathogenic role in SLE associated with epilepsy.

Changes in electroencephalographic characteristics and blood-brain barrier permeability in WAG/Rij rats with cortical dysplasia.

PURPOSE: This study investigated the effects of cortical dysplasia (CD) on electrophysiology and blood-brain barrier (BBB) permeability in WAG/Rij rats with genetic absence epilepsy. METHODS: Pregnant WAG/Rij rats were exposed to 145cGy of gamma-irradiation on embryonic day 17 to induce CD. An electroencephalogram was recorded from cortices subdurally in the offspring of the pregnant animals. Horseradish peroxidase (HRP) was used as determinant of BBB permeability. RESULTS: A massive tissue loss in the cerebral cortex was seen in WAG/Rij rats with CD (p<0.05). There was a significant decrease in the number and duration of spike-and-wave discharges (SWDs) and an increase in the frequency of SWDs in the WAG/Rij rats with CD when compared with the properties of SWDs in intact WAG/Rij rats (p<0.01). Ultrastructurally, the accumulation of HRP reaction products in the cerebral cortex and thalamus of WAG/Rij rats was significantly higher than that of control values (p<0.01). The accumulation of HRP reaction products in the cerebral cortex and thalamus regions of WAG/Rij rats with CD increased and was higher than that of the control and WAG/Rij animals (p<0.01). CONCLUSION: In our study, we showed that number and duration of SWDs decreased and SWD frequency increased in WAG/Rij rats with CD, suggesting a shift in seizure pattern. The association of these alterations with significant loss of cortical thickness and increased BBB permeability to HRP tracer may represent a causal relation of the EEG abnormalities with cerebral structural changes in these animals.

How Different Are the Patients With Bilateral Hippocampal Sclerosis From the Unilateral Ones Clinically?

PURPOSE: There is a lack of knowledge on consecutive patients with epilepsy associated with bilateral hippocampal sclerosis (BHS). We aimed to investigate the differentiating features of BHS in comparison with unilateral HS (UHS). METHOD: We investigated our database for patients with epilepsy fulfilling the major magnetic resonance imaging criteria for BHS; namely, presence of bilateral atrophy and high signal changes on T2 and FLAIR series in the hippocampi. UHS patients seen in past 2 years were included as the control group. Clinical, EEG, and other laboratory findings, data on treatment response and epilepsy surgery were investigated from their files. RESULTS: A total of 124 patients (31 with BHS and 93 with UHS; 49 right-sided and 44 left-sided) were included. We found that 16.1% of the BHS and 18.3% of the UHS groups were not drug-refractory. A binary logistic regression analysis performed with significant clinical features disclosed that history of febrile status epilepticus, mental retardation, and status epilepticus were statistically more common in BHS group. Moreover, diagnosis of psychosis established by an experienced psychiatrist and slowing of the EEG background activity were both found significantly more frequent in BHS. 66.67% of the operated BHS patients showed benefit from epilepsy surgery. CONCLUSIONS: BHS is a heterogeneous group, showing significant differences such as increased frequencies of mental retardation, status epilepticus, febrile status epilepticus and psychosis, in comparison to UHS. In all, 16.1% of the BHS cases showed a benign course similar to the UHS group and some patients with drug-resistant epilepsy may show benefit from epilepsy surgery.

The effect of transcranial direct current stimulation on seizure frequency of patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVES: Transcranial direct current stimulation (tDCS) is a non-invasive and safe method tried in drug-resistant epilepsies, in recent years. Our aim was to evaluate the effect of tDCS in patients diagnosed with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) which is a well-known drug-resistant focal epilepsy syndrome. PATIENTS AND METHODS: Twelve MTLE-HS patients diagnosed with their typical clinical, EEG and MRI findings fulfilling the criteria for drug-resistance as suggested by the ILAE commission were included after Ethics Committee approval and their signed consent. All patients received modulated cathodal stimulation; 2mA for 30min on 3 consecutive days. All patients also received sham stimulation with the same electrode positions; designed as 60s stimulation gradually decreasing in 15s with placement of the electrodes for 30min over the stimulation side. They were followed up by standard seizure diaries and their medical treatment was not changed during the study period. Their seizure frequencies both before and after cathodal tDCS and sham stimulation were compared statistically. Adverse effects were also questioned. RESULTS: Mean age of our study group was 35.42±6.96 (6 males; median: 35.50). The mean seizure frequency was 10.58±9.91 (median=8; min-max=2-30) at the baseline and significantly decreased to 1.67±2.50 (median=0.5; min-max=0-8) after cathodal tDCS application (p=0.003). Ten patients (83.33%) had more than 50% decrease in their seizure frequencies after cathodal tDCS. Two patients (16.67%) also showed positive sham effect. Six patients (50%) were seizure-free in the post-cathodal tDCS period of one month. No adverse effect has been reported except tingling sensation during cathodal stimulation. CONCLUSION: Our small series suggested that cathodal tDCS may be used as an additional treatment option in MTLE-HS. It may be tried in TLE-HS patients waiting for or rejecting epilepsy surgery or even with ineffective surgery results. More studies are needed with large series of patients to investigate the effects of tDCS in drug resistant epilepsies.

Effects of beta-hydroxybutyrate on brain vascular permeability in rats with traumatic brain injury.

This study investigates the effect of beta-hydroxybutyrate (BHB) on blood-brain barrier (BBB) integrity during traumatic brain injury (TBI) in rats. Evans blue (EB) and horseradish peroxidase (HRP) were used as determinants of BBB permeability. Glutathione (GSH) and malondialdehyde (MDA) levels were estimated in the right (injury side) cerebral cortex of animals. The gene expression levels for occludin, glucose transporter (Glut)-1, aquaporin4 (AQP4) and nuclear factor-kappaB (NF-κB) were performed, and Glut-1 and NF-κB activities were analyzed. BHB treatment decreased GSH and MDA levels in intact animals and in those exposed to TBI (P<0.05). Glut-1 protein levels decreased in sham, BHB and TBI plus BHB groups (P<0.05). NF-κB protein levels increased in animals treated with BHB and/or exposed to TBI (P<0.05). The expression levels of occludin and AQP4 did not significantly change among experimental groups. Glut-1 expression levels increased in BHB treated and untreated animals exposed to TBI (P<0.05). While NF-κB expression levels increased in animals in TBI (P<0.01), a decrease was noticed in these animals upon BHB treatment (P<0.01). In animals exposed to TBI, EB extravasation was observed in the ipsilateral cortex regardless of BHB treatment. Ultrastructurally, BHB attenuated but did not prevent the presence of HRP in brain capillary endothelial cells of animals with TBI; moreover, the drug also led to the observation of the tracer when used in intact rats (P<0.01). Altogether, these results showed that BHB not only failed to provide overall protective effects on BBB in TBI but also led to BBB disruption in healthy animals.

Intravenous levetiracetam treatment in status epilepticus: A prospective study.

OBJECTIVE: To assess the efficacy of intravenous (IV) levetiracetam (LEV) in the treatment of status epilepticus (SE) and treatment outcomes. METHODS: This study was conducted on patients, who were classified according to the clinical characteristics of their seizures, in the emergency department, neurology, and other services of our hospital. Patients were administrated IV LEV for the treatment of their SE after failing to respond to IV diazepam. RESULTS: We prospectively investigated 30 patients, 16 females and 14 males whose ages ranged between 17 and 90 years (55.6 ± 19.6). Fourteen patients had convulsive SE (CSE), 11 had nonconvulsive SE (NCSE), and 5 had epilepsia partialis continua (EPC). The patients were given IV LEV with dosages ranging between 1000 and 4000 mg/day. Twenty-nine of the patients continued to receive LEV orally as maintenance treatment. The most common etiologies were cerebrovascular diseases (n = 7) and brain tumors (n = 6). SE was terminated in 23 (76.6%) patients. In the 12 months that followed SE, 9 of our patients (30%) died and 4 patients could not be contacted. Fifteen patients reported having no adverse effects, whereas three had mild adverse effects. No major adverse effects or complications causing disability were observed in twelve patients who were unconscious. CONCLUSION: Treatment with IV LEV is well-tolerated and effective both in focal and generalized SE. IV LEV has the combined advantage of efficacy, safety, and ease of use, which qualifies it to be the first choice after benzodiazepines (BZD) in the treatment of SE. This is the first prospective study of IV LEV treatment in status epilepticus and has the longest follow-up period, one year.

Investigation of neuronal autoantibodies in two different focal epilepsy syndromes.

OBJECTIVE: Neuronal antibodies have been identified in patients with seizures as the main or sole symptom. Our aim was to investigate the prevalence of these autoantibodies in patients with focal epilepsy of unknown cause (FEoUC) and in the group having mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). METHODS: We studied anti-neuronal antibodies of consecutive adult patients diagnosed with FEoUC and MTLE-HS in our epilepsy center. The clinical and laboratory features of antibody-positive patients were compared with those of seronegative patients. The responses to therapy have also been investigated. RESULTS: Sera from 81 patients with epilepsy were tested. We found antibodies against glycine receptor (GLY-R) in 5 (6.2%), contactin-associated protein 2 (CASPR-2) in 4 (4.9%), N-methyl-d-aspartate receptor (NMDA-R) in 2 (2.5%), and voltage-gated potassium channel (VGKC)-complex in 2 (2.5%) of our patients with epilepsy. Psychotic attacks and nonspecific magnetic resonance imaging (MRI) white matter changes (WMCs) showed significant associations in seropositive patients (p = 0.003 and p = 0.03, respectively). Poor drug-response rates and total seizure counts were also higher in the seropositive patients but without reaching statistical significance. Three seropositive patients with previous epilepsy surgery showed typical histopathologic results for MTLE-HS, but not inflammatory changes. Moreover, some patients harboring these antibodies partly benefited from immunotherapy. SIGNIFICANCE: We detected neuronal antibodies in one sixth of patients with focal epilepsy, GLY-R antibodies being the leading one. Psychosis or nonspecific MRI WMCs were frequent in the seropositive group. Our results suggested that relevant antibodies should be screened for a treatment possibility in these groups.

A quadruple examination of ictal EEG patterns in mesial temporal lobe epilepsy with hippocampal sclerosis: onset, propagation, later significant pattern, and termination.

PURPOSE: The purpose of this study was to analyze electrophysiological properties of four main stages of ictal patterns of patients with operated temporal lobe epilepsy related to hippocampal sclerosis. METHODS: We included 48 patients with temporal lobe epilepsy-hippocampal sclerosis. Seizures were classified according to their electrophysiological properties and surgical outcomes as seizure-free and not seizure-free. The EEGs with artifacts at the beginning were analyzed separately. RESULTS: The most frequent type of ictal onset patterns was rhythmic theta/alpha activity, which was correlated to seizure-free group, whereas "switch of lateralization" and "bitemporal asynchrony" correlated to not seizure-free group. When bilateral independent ictal propagation patterns emerged, seizures tended to predict the side of epileptogenic zone wrongly. As a later significant pattern, rhythmic theta/alpha activity lateralized the focus correctly. Seizure termination was significantly concordant with hippocampal sclerosis lateralization in the seizure-free group. CONCLUSION: Ictal onset pattern with rhythmic theta/alpha activity correlates well with seizure freedom. Morphology of later significant patterns was more important in determining the lateralization reliability than time of appearance. The EEGs with short artifacts at the beginning are seen to be valuable in presurgical evaluation. Lateralization of ictal termination ipsilateral to MRI indicates good prognosis after surgery. Scalp EEG monitoring helps predict epileptogenic zones and postsurgical outcomes.